Enhancement of disease response in an immune host has been observed in respiratory syncytial, measles and dengue infections of infants and children. One of these, the dengue shock syndrome (DSS), occurs at epidemic proportions in Southeast Asia. The syndrome occurs in children who are infected in sequence with two of four known types of dengue virus. It is also seen in primarily infected infants who are born under epidemiological circumstances suggesting that their mothers were immune to dengue during gestation. Recent studies give evidence for a single mechanism for DSS in both these sets of circumstances; non-neutralizing dengue antibody can mediate the infection of mononuclear phagocytes. This cell may be the major site of dengue viral replication, in vivo. Shock, which occurs during the stage of virus elimination is presumably the result of the interaction between infected mononuclear phagocytes and an immune response(s). It follows that such DSS features as thrombocytopenia, abnormalities in blood clotting, activated complement and increased vascular permeability derive from mediators released during this immunological reaction. Attempts will be made to elicit and identify components in the immune response to dengue infection in rhesus monkeys. Next, a search will be initiated for mediators of inflammation in cultures of immunologically attached dengue infected monkey and human monocytes. The absence of virus in the child dying of DSS and the prozone in age distribution of infant DSS resemble similar features in SIDS cases. Pathogenetic mechanisms which trigger shock in DSS and death in SIDS may be analogous. The investigation will include attempts to determine if respiratory syncytial and parainfluenza viruses replicate in human peripheral blood leukocytes and, if so, whether antibody enhances leukocyte infection.